US2003060612A1PendingUtilityA1

Compositions and methods for the diagnosis and treatment of tumor

Assignee: GENENTECH INCPriority: Oct 28, 1997Filed: Jun 22, 2001Published: Mar 27, 2003
Est. expiryOct 28, 2017(expired)· nominal 20-yr term from priority
C07K 14/4748C07K 2319/30A61K 38/00
46
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Claims

Abstract

The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . Isolated nucleic acid having at least 80% nucleic acid sequence identity to: 
 (a) a nucleotide sequence that encodes the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10);    (b) a nucleotide sequence that encodes the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (c) a nucleotide sequence that encodes the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), with its associated signal peptide;    (d) a nucleotide sequence that encodes the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (e) the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);    (f) the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);    (g) the full-length coding sequence of the cDNA deposited under any ATCC accession number shown in Table 7; or    (h) the complement of (a), (b), (c), (d), (e), (f), or (g).    
     
     
         2 . Isolated nucleic acid comprising: 
 (a) a nucleotide sequence that encodes the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO: 9), or FIG. 10 (SEQ ID NO:10);    (b) a nucleotide sequence that encodes the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (c) a nucleotide sequence that encodes the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), with its associated signal peptide;    (d) a nucleotide sequence that encodes the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (e) the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);    (f) the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);    (g) the full-length coding sequence of the cDNA deposited under any ATCC accession number shown in Table 7; or    (h) the complement of (a), (b), (c), (d), (e), (f), or (g).    
     
     
         3 . Isolated nucleic acid that hybridizes to: 
 (a) a nucleotide sequence that encodes the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10);    (b) a nucleotide sequence that encodes the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (c) a nucleotide sequence that encodes the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), with its associated signal peptide;    (d) a nucleotide sequence that encodes the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (e) the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);    (f) the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);    (g) the full-length coding sequence of the cDNA deposited under any ATCC accession number shown in Table 7; or    (h) the complement of (a), (b), (c), (d), (e), (f), or (g).    
     
     
         4 . The nucleic acid of  claim 3 , wherein the hybridization occurs under stringent conditions.  
     
     
         5 . The nucleic acid of  claim 3  which is an oligonucleotide of at least about 5 nucleotides in length.  
     
     
         6 . An expression vector comprising the nucleic acid of  claim 1 .  
     
     
         7 . The expression vector of  claim 6 , wherein said nucleic acid is operably linked to control sequences recognized by a host cell transformed with the vector.  
     
     
         8 . A host cell comprising the expression vector of  claim 7 .  
     
     
         9 . The host cell of  claim 8  which is a CHO cell, an  E. coli  cell or a yeast cell.  
     
     
         10 . A process for producing a polypeptide comprising culturing the host cell of  claim 8  under conditions suitable for expression of said polypeptide and recovering said polypeptide from the cell culture.  
     
     
         11 . An isolated polypeptide having at least 80% amino acid sequence identity to: 
 (a) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10);    (b) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (c) the amino acid sequence of the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), with its associated signal peptide;    (d) the amino acid sequence of the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (e) an amino acid sequence encoded by the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);    (f) an amino acid sequence encoded by the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5); or    (g) an amino acid sequence encoded by the full-length coding sequence of the cDNA deposited under any ATCC accession number shown in Table 7.    
     
     
         12 . An isolated polypeptide comprising: 
 (a) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10);    (b) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (c) the amino acid sequence of the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), with its associated signal peptide;    (d) the amino acid sequence of the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (e) an amino acid sequence encoded by the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);    (f) an amino acid sequence encoded by the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5); or    (g) an amino acid sequence encoded by the full-length coding sequence of the cDNA deposited under any ATCC accession number shown in Table 7.    
     
     
         13 . A chimeric polypeptide comprising the polypeptide of  claim 11  fused to a heterologous polypeptide.  
     
     
         14 . The chimeric polypeptide of  claim 13 , wherein said heterologous polypeptide is an epitope tag sequence or an Fe region of an immunoglobulin.  
     
     
         15 . An isolated antibody which binds to a polypeptide having at least 80% amino acid sequence identity to: 
 (a) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10);    (b) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (c) the amino acid sequence of the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), with its associated signal peptide;    (d) the amino acid sequence of the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;    (e) an amino acid sequence encoded by the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);    (f) an amino acid sequence encoded by the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5); or    (g) an amino acid sequence encoded by the full-length coding sequence of the cDNA deposited under any ATCC accession number shown in Table 7.    
     
     
         16 . The antibody of  claim 15  which binds to a polypeptide comprising: 
 (a) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10);  
 (b) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;  
 (c) the amino acid sequence of the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), with its associated signal peptide;  
 (d) the amino acid sequence of the extracellular domain of the polypeptide shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10), lacking its associated signal peptide;  
 (e) an amino acid sequence encoded by the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5);  
 (f) an amino acid sequence encoded by the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5); or  
 (g) an amino acid sequence encoded by the full-length coding sequence of the cDNA deposited under any ATCC accession number shown in Table 7.  
 
     
     
         17 . The antibody of  claim 15  which is a monoclonal antibody.  
     
     
         18 . The antibody of  claim 15  which is an antibody fragment.  
     
     
         19 . The antibody of  claim 15  which is a chimeric or a humanized antibody.  
     
     
         20 . The antibody of  claim 15  which is conjugated to a growth inhibitory agent.  
     
     
         21 . The antibody of  claim 15  which is conjugated to a cytotoxic agent.  
     
     
         22 . The antibody of  claim 21 , wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.  
     
     
         23 . The antibody of  claim 21 , wherein the cytotoxic agent is a toxin.  
     
     
         24 . The antibody of  claim 23 , wherein the toxin is selected from the group consisting of maytansinoid an d calicheamicin.  
     
     
         25 . The antibody of  claim 23 , wherein the toxin is a maytansinoid.  
     
     
         26 . The antibody of  claim 15  which is produced in bacteria.  
     
     
         27 . The antibody of  claim 15  which is produced in CHO cells.  
     
     
         28 . The antibody of  claim 15  which induces death of a cell to which it binds.  
     
     
         29 . The antibody of  claim 15  which is detectably labeled.  
     
     
         30 . An isolated nucleic acid comprising a nucleotide sequence that encodes the antibody of  claim 15 .  
     
     
         31 . An expression vector comprising the nucleic acid of  claim 30  operably linked to control sequences recognized by a host cell transformed with the vector.  
     
     
         32 . A host cell comprising the expression vector of  claim 31 .  
     
     
         33 . The host cell of  claim 32  which is a CHO cell, an  E. coli  cell or a yeast cell.  
     
     
         34 . A process for producing an antibody comprising culturing the host cell of  claim 32  under conditions suitable for expression of said antibody and recovering said antibody from the cell culture.  
     
     
         35 . A composition of matter comprising: 
 (a) the polypeptide of  claim 11;     (b) the chimeric polypeptide of  claim 13;  or    (c) the antibody of  claim 15 , in combination with a carrier.    
     
     
         36 . The composition of matter of  claim 35 , wherein said carrier is a pharmaceutically acceptable carrier.  
     
     
         37 . An article of manufacture: 
 (a) a container; and    (b) the composition of matter of  claim 35  contained within said container.    
     
     
         38 . The article of manufacture of  claim 37  further comprising a label affixed to said container, or a package insert included with said container, referring to the use of said composition of matter for the therapeutic treatment of or the diagnostic detection of a cancer.  
     
     
         39 . A method of killing a cancer cell that expresses a polypeptide having at least 80% amino acid sequence identity to: 
 (a) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10); or    (b) an amino acid sequence encoded by the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5), said method comprising contacting said cancer cell with an antibody that binds to said polypeptide on said cancer cell, thereby killing said cancer cell.    
     
     
         40 . The method of  claim 39 , wherein said antibody is a monoclonal antibody.  
     
     
         41 . The method of  claim 39 , wherein said antibody is an antibody fragment.  
     
     
         42 . The method of  claim 39 , wherein said antibody is a chimeric or a humanized antibody.  
     
     
         43 . The method of  claim 39 , wherein said antibody is conjugated to a growth inhibitory agent.  
     
     
         44 . The method of  claim 39 , wherein said antibody is conjugated to a cytotoxic agent.  
     
     
         45 . The method of  claim 44 , wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.  
     
     
         46 . The method of  claim 44 , wherein the cytotoxic agent is a toxin.  
     
     
         47 . The method of  claim 46 , wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin.  
     
     
         48 . The method of  claim 46 , wherein the toxin is a maytansinoid.  
     
     
         49 . The method of  claim 39 , wherein said antibody is produced in bacteria.  
     
     
         50 . The method of  claim 39 , wherein said antibody is produced in CHO cells.  
     
     
         51 . The method of  claim 39 , wherein said cancer cell is further exposed to radiation treatment or a chemotherapeutic agent.  
     
     
         52 . The method of  claim 39 , wherein said cancer cell is selected from the group consisting of a breast cancer cell, a colorectal cancer cell, a lung cancer cell, an ovarian cancer cell, a central nervous system cancer cell, a liver cancer cell, a bladder cancer cell, a pancreatic cancer cell, a cervical cancer cell, a melanoma cell and a leukemia cell.  
     
     
         53 . The method of  claim 39 , wherein said cancer cell overexpresses said polypeptide as compared to a normal cell of the same tissue origin.  
     
     
         54 . A method of therapeutically treating a mammal having a tumor comprising cells that express a polypeptide having at least 80% amino acid sequence identity to: 
 (a) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10); or    (b) an amino acid sequence encoded by the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5), said method comprising administering to said mammal a therapeutically effective amount of an antibody that binds to said polypeptide, thereby effectively treating said mammal.    
     
     
         55 . The method of  claim 54 , wherein said antibody is a monoclonal antibody.  
     
     
         56 . The method of  claim 54 , wherein said antibody is an antibody fragment.  
     
     
         57 . The method of  claim 54 , wherein said antibody is a chimeric or a humanized antibody.  
     
     
         58 . The method of  claim 54 , wherein said antibody is conjugated to a growth inhibitory agent.  
     
     
         59 . The method of  claim 54 , wherein said antibody is conjugated to a cytotoxic agent.  
     
     
         60 . The method of  claim 59 , wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.  
     
     
         61 . The method of  claim 59 , wherein the cytotoxic agent is a toxin.  
     
     
         62 . The method of  claim 61 , wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin.  
     
     
         63 . The method of  claim 61 , wherein the toxin is a maytansinoid.  
     
     
         64 . The method of  claim 54 , wherein said antibody is produced in bacteria.  
     
     
         65 . The method of  claim 54 , wherein said antibody is produced in CHO cells.  
     
     
         66 . The method of  claim 54 , wherein said tumor is further exposed to radiation treatment or a chemotherapeutic agent.  
     
     
         67 . The method of  claim 54 , wherein said tumor is a breast tumor, a colorectal tumor, a lung tumor, an ovarian tumor, a central nervous system tumor, a liver tumor, a bladder tumor, a pancreatic tumor, or a cervical tumor.  
     
     
         68 . A method of determining the presence of a polypeptide in a sample suspected of containing said polypeptide, wherein said polypeptide has at least 80% amino acid sequence identity to: 
 (a) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10); or    (b) an amino acid sequence encoded by the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5), said method comprising exposing said sample to an antibody that binds to said polypeptide and determining binding of said antibody to said polypeptide in said sample.    
     
     
         69 . The method of  claim 68 , wherein said sample comprises a cell suspected of expressing said polypeptide.  
     
     
         70 . The method of  claim 69 , wherein said cell is a cancer cell.  
     
     
         71 . The method of  claim 68 , wherein said antibody is detectably labeled.  
     
     
         72 . A method of diagnosing the presence of a tumor in a mammal, said method comprising detecting the level of expression of a gene encoding a polypeptide having at least 80% amino acid sequence identity to: 
 (a) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10); or    (b) an amino acid sequence encoded by the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5), in a test sample of tissue cells obtained from said mammal and in a control sample of known normal cells of the same tissue origin, wherein a higher level of expression of said polypeptide in the test sample, as compared to the control sample, is indicative of the presence of tumor in the mammal from which the test sample was obtained.    
     
     
         73 . The method of  claim 72 , wherein the step detecting the level of expression of a gene encoding said polypeptide comprises employing an oligonucleotide in an in situ hybridization or RT-PCR analysis.  
     
     
         74 . The method of  claim 72 , wherein the step detecting the level of expression of a gene encoding said polypeptide comprises employing an antibody in an immunohistochemistry analysis.  
     
     
         75 . A method of diagnosing the presence of a tumor in a mammal, said method comprising contacting a test sample of tissue cells obtained from said mammal with an antibody that binds to a polypeptide having at least 80% amino acid sequence identity to: 
 (a) the amino acid sequence shown in FIG. 6 (SEQ ID NO:6), FIG. 7 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:9), or FIG. 10 (SEQ ID NO:10); or    (b) an amino acid sequence encoded by the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3), FIG. 4 (SEQ ID NO:4), or FIG. 5 (SEQ ID NO:5), and detecting the formation of a complex between said antibody and said polypeptide in the test sample, wherein the formation of a complex is indicative of the presence of a tumor in said mammal.    
     
     
         76 . The method of  claim 75 , wherein said antibody is detectably labeled.  
     
     
         77 . The method of  claim 75 , wherein said test sample of tissue cells is obtained from an individual suspected of having a cancerous tumor.

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